Relationship between dysplasia, p53 protein accumulation, DNA ploidy, and Glut1 overexpression in Barrett metaplasia.

BACKGROUND: There is a need for molecular markers of malignant progression in Barrett metaplasia (BM). The aim of this study is to determine the relationship between dysplasia, p53 protein accumulation, DNA ploidy, and Glut1 in BM. METHODS: Sections of esophageal biopsy specimens from 120 patients with BM were evaluated for dysplasia, p53 protein, and Glut1 expression by immunohistochemistry, and DNA ploidy by Feulgen stain and image analysis. In cases with diploid DNA histograms, the percentage cells in the G0G1 and G2M phases of the cell cycle were determined. RESULTS: Of 108 diploid cases 19 (28%) of 69 cases with G0G1 > or = 90% or G2M > or = 8.33% were p53-positive, in contrast to only 1 (3%) of 39 cases with lower G0G1 or G2M (P = 0.0008). Of 32 p53-positive cases 11 (32%) were aneuploid, in contrast to none (0%) of 88 p53-negative cases (P < 0.0001). Ten (91%) of 11 aneuploid cases were high-grade dysplasial adenocarcinoma (HGD/CA), compared with only 1 (1%) of 109 diploid cases (P < 0.0001). Five (45%) of 11 cases with HGD/CA were Glut1-positive, in contrast to none (0%) of 109 cases without HGD/CA (P < 0.0001). CONCLUSIONS: Our data strongly suggest that in BM, after oxidative DNA damage, as a result of gastroesophageal reflux, there is an increase in the percentage of cells in the G0G1 or G2M phases of the cell cycle to enable repair of damaged DNA; in some of these cases this is followed sequentially by p53 gene mutation and protein accumulation, DNA aneuploidy, HGD, and CA with or without Glut1 overexpression. These events can be detected in routinely processed biopsy samples.

Membranous glomerulonephritis in diabetic patients: a study of 15 cases and review of the literature.

Glomerular diseases other than diabetic glomerulosclerosis (DGS) occurring in diabetic patients may pose a diagnostic challenge to both clinicians and pathologists. We studied 15 cases of membranous glomerulonephritis (MG) in patients with diabetes mellitus focusing on the morphologic changes of the kidney. Light microscopic observation revealed nodular and/or diffuse DGS in 12 cases and no DGS in three. Periodic acid-silver methenamine stain showed spikes or chain-like structures in the glomerular capillary wall in 13 cases, indicating the presence of MG. Ultrastructurally, MG was classified into Stage I (N = 2), II (N = 8), III (N = 4), or IV (N = 1). Six out of nine cases with Stages I and II MG showed a thickened lamina densa of the glomerular basement membrane (GBM), suggesting diabetic influence on the GBM. Moreover, MG in some of the cases suggested atypical ultrastructural features including (a) the presence of large immune type deposits separated by tall spikes (N = 4), (b) high electron density of deposits in spite of their intramembranous location (N = 4), and (c) the presence of immune type deposits of mesangial (N = 3) and subendothelial (N = 2) locations. It is postulated that these atypical features are caused by altered turnover of the GBM, impaired glomerular clearance of immune complexes, changes of the glomerular capillary wall as the result of hemodynamic alterations, and/or nonenzymatic glycosylation in diabetic milieu.

Mucinous islet cell (amphicrine) carcinoma of the pancreas associated with watery diarrhea and hypokalemia syndrome.

A case of mucinous islet cell carcinoma associated with watery diarrhea and hypokalemia syndrome is reported. Electron microscopic and immunohistochemical studies demonstrated mucigen granules and endocrine features in the tumor cells. The significance of the findings with regard to the histogenesis and diagnosis of this rare neoplasm is discussed.